In order to augment the durability of anti–PD-1 treatment, it was combined with anti–CTLA-4. The combined treatment group had a better memory antitumor response compared with anti–PD-1 alone.

Some T cells have excellent memories. These subtypes—known as memory T cells—may explain why some immunotherapies are more effective than others and could potentially lead to researchers designing more effective studies using combination checkpoint blockade treatments, according to investigators at The University of Texas MD Anderson Cancer Center.

Their study demonstrated that anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) and anti–programmed cell death protein 1 (PD-1) immunotherapies together appear to enhance response rates and generate the formation of memory T cells in mice vaccinated with melanoma cells. The combination could explain why relapse occurs in some patients with therapies targeting CTLA-4 and PD-1 checkpoints, which evade the body’s immune system.

“We are learning more about the differences between anti–CTLA-4 and anti–PD-1 therapies,” said Stephen Mok, PhD, Postdoctoral Fellow of Immunology, who presented the findings. “We know that while anti–PD-1 therapy produces a greater response rate than anti–CTLA-4, one issue is the durability of the responses.”

Response Rates

Patients who receive anti–PD-1 treatment have an average response rate of 30%, but approximately 25% of the patients experience tumor relapse within 2 years after treatment has stopped. Patients treated with anti–CTLA-4 have a response rate of 11%, with 22% of patients surviving at least 10 years.

The team took a closer look at memory T cells, which in previous bacteria and virus studies have suggested anti–CTLA-4 increases memory T-cell levels. Conversely, anti–PD-1 tends to reduce their formation.

Memory T cells are immune cells that previously have encountered cancer and gained the ability to recognize cancer antigens and reproduce more quickly, resulting in a faster and stronger defense. The investigators vaccinated mice with irradiated melanoma cells and treated them with either anti–CTLA-4 or anti–PD-1 to see if there were differences in memory T-cell formation.

Preclinical Findings

“Although both anti–CTLA-4 and anti–PD-1 improved tumor rejection, mice treated with anti–CTLA-4 exhibited superior tumor control, suggesting the memory T-cell response by this agent is more durable,” said Dr. Allison. “In order to augment the durability of anti–PD-1 treatment, it was combined with anti–CTLA-4. What we found was that the combined treatment group had a better memory antitumor response compared with anti–PD-1 alone.”

The team reported that collectively their findings facilitate the design of combination immunotherapy treatments that enhance both response rates and generation of memory T cells to prevent relapse.

“Understanding how checkpoint blockade therapies affect memory T-cell development opens up the possibilities for refining current combination immunotherapy treatments and improving patient outcomes,” said Dr. Mok.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.